アルツハイマー病のプロテオミクス

抄録

Quantitative proteome analysis was performed in Alzheimer disease brain with 2-D gel to identify disease specific changes in protein expression. These changes were also investigated in serum and urine of Alzheimer patients. The task of characterizing the proteome and its components is now practically achievable because of the development and integration of four important tools; complete genome sequence databases, mass spectrometry, matching software for protein sequences and protein separation technology. Mass spectrometry instrumentation has undergone tremendous change over the past decade, culminating in the development of highly sensitive, robust instruments that can reliably analyze biomolecules, particularly proteins and peptides. In brain protein separation, we sequentially extracted them using two distinct sample solutions, yielding different protein fractions. These fractions showed distinct 2-DE patterns with high resolution and excellent reproducibility. In soluble fraction, approximately 1300 protein spots were detected, and five spots are significantly increased and 10 spots are significantly decreased in AD. The proteins identified include enzymes, molecular chaperones and cytoskeletal proteins. In low soluble fraction, over 500 protein spots were detected in the 2-DE data analysis. There were three spots significantly increased in AD. Two of these spots were identified as glial fibrillary acidic protein using mass spectrometry. These findings prompt further study on disease-linked proteins for the investigation of AD pathogenesis and for the quest of disease markers in serum and urine.